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Gene Section
Review
RUNX1 (runt-related transcription factor 1 (acute
myeloid leukemia 1; aml1 oncogene))
Jean-Loup Huret, Sylvie Senon
Genetics, Dept Medical Information, UMR 8125 CNRS, University of Poitiers, CHU Poitiers Hospital, F86021 Poitiers, France (JLH, SS)
Published in Atlas Database: January 2003
Online updated version: http://AtlasGeneticsOncology.org/Genes/AML1.html
DOI: 10.4267/2042/37948
This article is an update of : AML1 (acute myeloid leukemia 1). RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1;
aml1 oncogene)). Atlas Genet Cytogenet Oncol Haematol.1997;1(2):59-61.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2003 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
DNA Diagram.
Other names: AML1 (acute myeloid leukemia 1);
CBFA2 (core binding factor A2); PEBPaB
(polyomavirus enhancer binding protein aB)
HGNC (Hugo): RUNX1
Location: 21q22.3
Transcription
transcription is from telomere to centromere --> the
fusion gene is located on the 'other' chromosome (eg
the der(8) of the t(8;21), the der(3) of the t(3;21)...);
alternate splicing --> transcripts of 2, 3.3, -> 7.5 and 8
kb.
Protein
Description
250, 453 amino acids and other forms; forms
heterodimers with CBFB.
AML1 (21q22.3) in normal cells: clone dJ1107L6 - Courtesy
Mariano Rocchi, Resources for Molecular Cytogenetics.
Expression
DNA/RNA
Widely expressed, including hematopoietic cells at
various
stages
of
differenciation:
role
in
haematopoiesis.
Description
Localisation
the gene spans a region of more than 120 kb.
Nuclear.
Protein Diagram.
Atlas Genet Cytogenet Oncol Haematol. 2003; 7(2)
98
RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
t(8;21;Var) are known and have revealed that the
crucial event lies on der(8); in agrement with the fact
that both genes are transcribed from telomere to
centromere.
Hybrid/Mutated gene
5' AML - 3' ETO.
Abnormal protein
N-term AML1 with the Runt domain fused to the
nearly entire ETO.
Oncogenesis
the fusion protein retain the ability to recognize the
AML1 concensus binding site (--> negative dominant
competitor with the normal AML1) and to dimerize
with the cbtb/CBTB subunit --> probable altered
transcriptional regulation of normal AML1 target
genes.
Function
Transcription
factor
(activator)
for
various
hematopoietic-specific genes: binds to the core site 5'
PyGPyGGTPy 3' of a number of promotors and
enhancers, as in GM-CSF (granulocyte-macrophage
colony stimulating factor), CSF1R (colony stimulating
factor 1 receptor), TCRb sites (T cell antigen
receptors), and myeloid myeloperoxidase.
Homology
1- Runt (drosophila): nuclear DNA binding protein;
role in segmentation (embryology);
2- AML2 (also called: CBFA3, CBFa3, PEBPaC),
located in 1p35-36, expressed in B lineage (3 and 5 kb
RNA); AML3: (also called: CBFA1, CBFa1, PEBPaA)
in 6p21;
3- cbfa family (mouse).
t(8;21)(q23;q22) MDS --> FOG2 / AML1
t(8;21)(q24;q22) ALL and ANLL -->
TRPS1 / AML1
t(12;21)(p13;q22)/ALL --> ETV6-AML1
Implicated in
Familial platelet disorder with
predisposition to acute non
lymphocytic leukemia
t(1;21)(p36;q22) treatment related acute
non lymphocytic leukemia (ANLL) --> ?/
AML1
t(2;21)(p11;q22) ANLL --> ?/ AML1
t(3;21)(q26;q22)/ myelodysplastic
syndrome (MDS) or ANLL --> -EVI1 or
EAP/ MDS1 - AML1
Disease
B cell ALL (CD10+).
Prognosis
CR in all cases; prognosis seems good.
Cytogenetics
Often undetectable without FISH; additional
anomalies: frequent del(12)(p12) on the other allele.
Hybrid/Mutated gene
5' ETV6 - 3' AML1on the der(21).
Abnormal protein
Helix loop helix of TEL fused to the nearly entire
AML1 protein; the other TEL allele is often deleted.
Disease
CML-BC of myeloid type; ANLL and MDS, often
therapy related (secondary to antitopoisomerase II).
Hybrid/Mutated gene
5' AML1 - 3' EAP or MDS1 or EVI1.
t(12;21)(q24;q22) ANLL --> ?/ AML1
t(16;21)(q24;q22) ANLL --> MTG16-AML1
t(4;21)(q31;q22) T-cell acute
lymphoblastic leukemia (T-ALL) --> ?/
AML1
t(5;21)(q13;q22) myelodysplastic
syndrome (MDS) and ANLL --> ?/ AML1
t(8;21)(q22;q22)/ANLL. --> ETO - AML1
Disease
ANLL and therapy related ANLL; mainly with
preceeding MDS
Prognosis
Very poor.
t(17;21)(q11;q22) ANLL
t(19;21)(q13;q22) treatment related
ANLL --> AMP19 / AML1
t(20;21)(q1;3q22) treatment related ANL
--> ? / AML1
t(21;21)(q11;q22) MDS --> UPS25 / AML1
Disease
ANLL, M2 mostly.
Prognosis
CR is obtained; median survival (1.5-2 yrs) is the range
with other ANLL or relatively better.
Cytogenetics
additional anomalies are frequent: loss of Y or X
chromosome, del(7q)/-7, +8, del (9q); complex
Atlas Genet Cytogenet Oncol Haematol. 2003; 7(2)
Huret JL, Senon S
99
RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Huret JL, Senon S
Breakpoints
21q11 (UPS25)
20q13
Familial
platelet
disorder
1p36
1p13
2p11
2q21
19q13(AMP19)
3q26 (EAP/MDS1/EVI1)
18q21
4q21
4q31
17q11
5q13
16q24 (MTG16)
21q22(AML1)
6p22
15q22
8q13
14q24
8q22 (ETO)
14q22
8q23 (FOG2)
14q13
8q24 (TRPS1)
12q24
12p13 (ETV6)
9p21
11p13
10q21
AML1 and partners - recurrent translocations. Editor 02/2003; updated 08/2003.
Note: cases of AML1 translocations with either 4q21, 4q27, 8q24 (not the TRPS1 one), 11q24,14q11,
16p13 hav e been prov ed to be cry ptic t(12;21) with ETV6/AML1 inv olv ement, and we hav e theref ore
to be cautious with breakpoints without a partner described.
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Huret JL, Senon S
This article should be referenced as such:
Huret JL, Senon S. RUNX1 (runt-related transcription
factor 1 (acute myeloid leukemia 1; aml1 oncogene)). Atlas
Genet Cytogenet Oncol Haematol. 2003; 7(2):98-101.
101